Tumour budding-based grading as independent prognostic biomarker in HPV-positive and HPV-negative head and neck cancer

Stögbauer, Fabian; Beck, Susanne; Ourailidis, Iordanis; Heß, Jochen; Poremba, Christopher; Lauterbach, Maren; Wollenberg, Barbara; Buchberger, Anna Maria Stefanie; Jesinghaus, Moritz; Schirmacher, Peter; Weichert, Wilko; Boxberg, Melanie; Budczies, Jan

doi:10.1038/s41416-023-02240-y

Cited by 12 publications

(13 citation statements)

References 63 publications

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“…Moreover, despite ITBCC recommended adopting a three-tier score system (low risk ≤4 buds; intermediate risk 5-9 buds; high risk ≥10 buds) to perform risk stratification, most of the studies discussed herein adopted a two-tier score system with a cut-off point of five buds (low risk <5 buds vs. high risk ≥5 buds), while only four studies maintained the three-tier score system. 34,44,56,60 Generally, the 5 buds cut-off seemed to be an appropriate discriminator to stratify patients; however, further studies are needed to validate these data. 20 The evaluation of TB in preoperative biopsies is an aspect less investigated in HNSCC.…”

Section: The Pathological Evaluation Of Tumor Budding In Hnsccmentioning

confidence: 96%

“…The median number of patients per study was 150 (range 53-254 cases). Histopathological analysis was based on biopsies in 4 studies (11.1%), 38,[45][46][47] on surgical specimens in 30 (83.3%), [30][31][32][33][35][36][37][39][40][41][42][43][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] and mixed bioptic samples/surgical specimens in 2 (5.55%). 34,44 Major findings of the retrieved articles are discussed in dedicated paragraphs of section 4.…”

Section: Included Studies' Characteristicsmentioning

confidence: 99%

“…5,87 In a multivariate analysis, the new grading system seemed to be the only one with a significant prognostic role. 56 Moreover, they studied the correlation between TB and neck lymph node metastasis in cN0 patients, thus suggesting the role of TB in identifying lymph nodes with an elevated risk of micro-metastasis and highlighting the importance of this finding in the decision making for surgical treatment planning. In addition, they hypothesized that small tissue areas that can be analyzed for TB under 1 HPF could be transferable to an excisional biopsy sample.…”

Section: Tumor Budding In Non-oral Hnsccmentioning

confidence: 99%

“…In addition, they hypothesized that small tissue areas that can be analyzed for TB under 1 HPF could be transferable to an excisional biopsy sample. 56 The prognostic role of TB in LSCC was initially studied in 2010 by Sarioglu et al 53 who analyzed a sample of 64 patients with LSCC. In this series, N+ status and higher TB scores were significantly associated with distant metastasis in LSCC.…”

Section: Tumor Budding In Non-oral Hnsccmentioning

confidence: 99%

“…A recent investigation by Stögbauer et al 56 suggested an improved histopathological grading system that for the first time was comprehensive of both HPV positive and negative HNSCC. In particular, they analyzed the prognostic significance of TB and CNS and stratified tumors in two subgroups of cellular dissociation grading according to budding levels.…”

Section: Tumor Budding In Non-oral Hnsccmentioning

confidence: 99%

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Tumor budding to investigate local invasion, metastasis, and prognosis of head and neck carcinoma: A systematic review

Zanoletti,

Daloiso,

Nicolè

et al. 2023

Head & Neck

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The aim of this systematic review is to shed light on the role of tumor budding (TB) in the biology, behavior, and prognosis of head and neck squamous cell carcinoma (HNSCC). A search was run in PubMed, Scopus, and Embase databases following PRISMA guidelines. After full‐text screening and application of inclusion/exclusion criteria, 36 articles were included. Several investigations support the prognostic role of TB, which might play a role in selecting rational treatment strategies. To achieve this goal, further research is needed for greater standardization in TB quantification. Although TB is not included as a negative prognostic factor in the current management guidelines, it might be reasonable to consider a closer follow‐up for HNSCC cases with high histopathological evidence of TB.

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Section: The Pathological Evaluation Of Tumor Budding In Hnsccmentioning

confidence: 96%

Section: Included Studies' Characteristicsmentioning

confidence: 99%

Section: Tumor Budding In Non-oral Hnsccmentioning

confidence: 99%

Section: Tumor Budding In Non-oral Hnsccmentioning

confidence: 99%

Section: Tumor Budding In Non-oral Hnsccmentioning

confidence: 99%

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Tumor budding to investigate local invasion, metastasis, and prognosis of head and neck carcinoma: A systematic review

Zanoletti,

Daloiso,

Nicolè

et al. 2023

Head & Neck

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The modified Polsby–Popper score, a novel quantitative histomorphological biomarker and its potential to predict lymph node positivity and cancer‐specific survival in oral tongue squamous cell carcinoma

Csűry,

Balk

et al. 2023

Cancer Medicine

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BackgroundThe significance of different histological spreading patterns of tumor tissue in oral tongue squamous cell carcinoma (TSCC) is well known. Our aim was to construct a numeric parameter on a continuous scale, that is, the modified Polsby–Popper (MPP) score, to describe the aggressiveness of tumor growth and infiltration, with the potential to analyze hematoxylin and eosin‐stained whole slide images (WSIs) in an automated manner. We investigated the application of the MPP score in predicting survival and cervical lymph node metastases as well as in determining patients at risk in the context of different surgical margin scenarios.MethodsWe developed a semiautomated image analysis pipeline to detect areas belonging to the tumor tissue compartment. Perimeter and area measurements of all detected tissue regions were derived, and a specific mathematical formula was applied to reflect the perimeter/area ratio in a comparable, observer‐independent manner across digitized WSIs. We demonstrated the plausibility of the MPP score by correlating it with well‐established clinicopathologic parameters. We then performed survival analysis to assess the relevance of the MPP score, with an emphasis on different surgical margin scenarios. Machine learning models were developed to assess the relevance of the MPP score in predicting survival and occult cervical nodal metastases.ResultsThe MPP score was associated with unfavorable tumor growth and infiltration patterns, the presence of lymph node metastases, the extracapsular spread of tumor cells, and higher tumor thickness. Higher MPP scores were associated with worse overall survival (OS) and tongue carcinoma‐specific survival (TCSS), both when assessing all pT‐categories and pT1‐pT2 categories only; moreover, higher MPP scores were associated with a significantly worse TCSS in cases where a cancer‐free surgical margin of <5 mm could be achieved on the main surgical specimen. This discriminatory capacity remained constant when examining pT1‐pT2 categories only. Importantly, the MPP score could successfully define cases at risk in terms of metastatic disease in pT1‐pT2 cancer where tumor thickness failed to exhibit a significant predictive value. Machine learning (ML) models incorporating the MPP score could predict the 5‐year TCSS efficiently. Furthermore, we demonstrated that machine learning models that predict occult cervical lymph node involvement can benefit from including the MPP score.ConclusionsWe introduced an objective, quantifiable, and observer‐independent parameter, the MPP score, representing the aggressiveness of tumor growth and infiltration in TSCC. We showed its prognostic relevance especially in pT1‐pT2 category TSCC, and its possible use in ML models predicting TCSS and occult lymph node metastases.

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TGFβ‐induced EN1 promotes tumor budding of adenoid cystic carcinoma in patient‐derived organoid model

Hui,

Wang,

Liu

et al. 2024

Intl Journal of Cancer

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Adenoid cystic carcinoma (ACC) and basal cell adenoma (BCA) share many histological characteristics and often need a differential diagnosis in clinical pathology. Recently, we found homeobox protein engrailed‐1 (EN1) was a potential diagnostic marker for ACC in an organoids library of salivary gland tumors (SGTs). Here we aim to confirm EN1 as a differential diagnostic marker for ACC, and further investigate the regulatory mechanism and biological function of EN1 in tumor progression. The transcriptional analysis, quantitative polymerase chain reaction, Western blot and immunohistochemistry staining were performed and revealed that EN1 was specifically and highly expressed in ACC, and accurately differentiated ACC from BCA. Furthermore, TGFβ signaling pathway was found associated with ACC, and the regulation of EN1 through TGFβ was detected in the human ACC cell lines and patient‐derived organoids (PDOs). TGFβ‐induced EN1 was important in promoting tumor budding in the PDOs model. Interestingly, a high level of EN1 and TGFβ1 in the budding tips was observed in ACC clinical samples, and the expression of EN1 and TGFβ1 in ACC was significantly associated with the clinical stage. In summary, our study verified EN1 is a good diagnostic marker to differentiate ACC from BCA. TGFβ‐induced EN1 facilitates the tumor budding of ACC, which might be an important mechanism related to the malignant phenotype of ACC.

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Tumour budding-based grading as independent prognostic biomarker in HPV-positive and HPV-negative head and neck cancer

Cited by 12 publications

References 63 publications

Tumor budding to investigate local invasion, metastasis, and prognosis of head and neck carcinoma: A systematic review

Tumor budding to investigate local invasion, metastasis, and prognosis of head and neck carcinoma: A systematic review

The modified Polsby–Popper score, a novel quantitative histomorphological biomarker and its potential to predict lymph node positivity and cancer‐specific survival in oral tongue squamous cell carcinoma

TGFβ‐induced EN1 promotes tumor budding of adenoid cystic carcinoma in patient‐derived organoid model

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